Many compounds are known to treat disturbances of memory that occur in certain biological disorders. For example, the memory loss in Alzheimer's disease or senile dementia is associated with a malfunction of a cholinergic neuron. Therapies pertaining to alleviating such memory loss include attempts to increase the acetylcholine content in the brain by using an anti-acetylcholinesterase (see, e.g., Japanese Patent Documents 61-148154, 63-141980, 63-225358, 63-238063, 63-239271, 63-284175, 63-297367, 64-73 and 1-132566, European Patent Application EP-A-268871, and International (PCT) Published Application WO 88/02256).
U.S. Pat. No. 5,397,785 discloses a class of 4-acylaminopyridine derivatives that activate malfunctioned cholinergic neurons. Compounds and acid addition salts thereof disclosed in the '785 patent are believed to improve disturbances of memory by a different mechanism than conventional compounds known to have anti-acetylcholinesterase activity. However, of all the compounds disclosed therein, the '785 patent provides no discussion regarding polymorphs of any of the compounds.
The ability of a substance to crystallize with more than one crystal structure is known as polymorphism, and a particular crystal form is called a polymorph. Different polymorphs of the same compound can have quite different physical properties, such as shelf-life and solubility. Some of these differences in physical properties can lead to differences in efficacy.
Because of these differences, it is useful to know which particular polymorph or mixture of polymorphs is being used.
Unfortunately, the detection of various polymorph forms of a single drug substance is not always readily discemable. Moreover, once a specific polymorph is recognized and desired for its characteristics, researchers must discover how to prepare consistently pure quantities of the polymorph form. Methods of preparing pure forms of a polymorph are not trivial and can require intensive discovery efforts.
Therefore, a pure or essentially pure polymorph of a compound is desirable from the standpoint of being able to accurately characterize the physical properties and biological efficacy against certain disease states, such as, for example, a malfunctioned cholinergic neuron associated with memory loss. Moreover, methods that allow for the production of not just one pure polymorph, but two polymorphs of a compound, also are desirable. The invention provides such polymorph compounds and methods related thereto.